Project summary Nutritional status affects many aspects of physiology, including reproduction and cell proliferation. It is increasingly important to understand the effects of nutrition on cell behavior at the molecular level, since devastating diseases such as diabetes are linked to improper cellular responses to nutritional input. The proposed research will further the understanding of the connection between molecular pathways that respond to nutritional control and cell proliferation. Our studies will provide a deeper understanding of the relationships between nutritionally linked diseases such as diabetes and cell-proliferation diseases such as cancer, which occurs at a higher incidence in diabetic patients. The molecular mechanisms by which nutrition-sensitive molecular pathways control reproduction and cell proliferation are not well understood. The nematode C. elegans is an excellent model organism for studying the cellular effects of conserved nutritionally-responsive signaling pathways such as the insulin signaling pathway on germline cell proliferation in the context of a whole organism. Our recent results implicate the insulin pathway in germline proliferation in C. elegans, with specific effects on germline cell cycle. I am currently investigating the TOR-S6K pathway, another key nutrition-sensitive pathway that is thought to act in concert with the insulin signaling. My work addresses the following questions: What role does the TOR-S6K pathway play in germline proliferation? What is the connection to the insulin pathway? What are the downstream effectors of S6K for the germline phenotype? PUBLIC HEALTH RELEVANCE: Project Narrative Our long-term goal is to understand how nutritional status affects cell proliferation. Molecular pathways that respond to nutrition and that control cell cycle are conserved in all organisms. We are using a simple experimental system, the germ line of C. elegans as a model to investigate the connection between these fundamental processes that affect normal physiology and development as well as disease states.